The present invention relates to measuring and testing. More particularly, the present invention relates to measuring the concentration of at least one analyte with the aid of an oxidase of an immersion sensor situated in a fluid or in a matrix containing fluid. The matrix is preferably an organic tissue, for example, a human or animal tissue. In preferred applications or uses of the present invention, the immersion sensor is implanted into the tissue. Subcutaneously implantable micro-sensors, on the basis of glucose oxidase as a preferred example of an oxidase, represent some particularly preferred exemplary applications for the diagnosis and intensive treatment of diabetes. Other preferred applications of the immersion sensor include measuring oxidase substrates in fluids with a low oxygen content.
Amperometric enzyme sensors for analyzing individual samples on the basis of analyte-specific oxidases can be regarded as technically mature. By contrast, immersion sensors on the basis of a oxidase reaction, which are inserted or implanted into a fluid or matrix containing analyte, are still in the process of technical development. If the concentration of dissolved oxygen is below the analyte concentration, the necessary oxygen saturation of the oxidase can only be achieved by selectively obstructing the diffusion of the analyte. The problem of oxygen saturation is accentuated in hypoxic media. Subcutaneously implantable amperometric micro-sensors, on the basis of glucose oxidase, have a potential area of application for the diagnosis and intensive treatment of diabetes mellitus [Bindra, D. D., Zhang, Y., Wilson, G., Sternberg, R., Thevenot, D. R., Moatti, D., Reach, G.: Anal Chem 63, 17, 1692-1696, 1991, DCCT Research Group, N Engl. J. Med. 329, 977-986, 1993, Fischer, U., Rebrin, K., v. Woedtke, T., Abel, P.: Horm. Metab. Res. 26, 515-522, 1994; Zick, R., Schiewitz, J.: Diabetes aktuell 4, 38-40, 2000]. Since the concentration of dissolved oxygen in the tissue is only a few hundredths of the glucose concentration, the layer containing enzyme is covered by a membrane whose permeability to oxygen is about a thousand times higher than its permeability to glucose. This is achieved by using permselective membranes [Schneider, H., Streicher S.: Artif Organs 9 (2), 180-183, 1985; Ward R S, W. K.: U.S. Pat. No. 5,428,123], so-called analyte windows, i.e. unselective pores or perforations in an oxygen-permeable, analyte-impermeable membrane [Abel, P., Kautek, W., v. Woedtke, T., Krüger, J.: DE 195 47 923.8 (1999)] or by using a sensor with different membranes on each side of the enzyme layer, wherein one membrane is permeable with a low permeability to the analyte and the other is only permeable to oxygen [Gough et al., Anal. Chem. 57, 2351-2357, 1985]. Implantable amperometric glucose sensors currently require recalibrating at certain time intervals, because the sensitivity is reduced over time. One of the possible causes for this is regarded as being an increase in the diffusion resistance of the glucose due to permeation-inhibiting deposits on the membrane or the analyte window [Rigby et al., Anal. Chim. Acta 385, 23-32, 1999, Thome-Duret, V., Gangerau, M. N., Zhang, Y., Wilson, G. S., Reach, G.: Diabetes Metab 22 (3), 174-178].